Novel metabolites distinct from canonical pathways can be identified through the integration of three cheminformatics tools: BinVestigate, which queries the BinBase gas chromatography-mass spectrometry (GC-MS) metabolome database to match unknowns with biological metadata across over 110,000 samples; MS-DIAL 2.0, a software tool for chromatographic deconvolution of high-resolution GC-MS or liquid chromatography-mass spectrometry (LC-MS); and MS-FINDER 2.0, a structure-elucidation program that uses a combination of 14 metabolome databases in addition to an enzyme promiscuity library. We showcase our workflow by annotating N-methyl-uridine monophosphate (UMP), lysomonogalactosyl-monopalmitin, N-methylalanine, and two propofol derivatives.
Summary
NTB‐A is a CD2‐related cell surface protein expressed primarily on lymphoid cells including B‐lymphocytes from chronic lymphocytic leukaemia (CLL) and lymphoma patients. We have generated a series of monoclonal antibodies (mAbs) against NTB‐A and assessed their therapeutic potential for CLL. Selective mAbs to NTB‐A were further tested in functional complement‐dependent cytotoxicity (CDC) and antibody‐dependent cellular cytotoxicty (ADCC) assays in cell lines and B lymphocytes freshly isolated from CLL patients. While lower levels of NTB‐A were detected in T and natural killer (NK) cells, CDC activity was demonstrated primarily in B cells isolated from CLL patients and B lymphoma cell lines. Knockdown of NTB‐A by small interfering RNA in target cells results in lower cytotoxicity, demonstrating the specificity of the mAbs. Furthermore, anti NTB‐A mAbs demonstrated anti‐tumour activity against CA46 human lymphoma xenografts in nude mice and against systemically disseminated Raji human lymphoma cells in severe combined immunodeficient mice. Taken together, these results demonstrate NTB‐A as a potential new target for immunotherapy of leukaemia and lymphomas.
The Static 99R is an actuarial instrument that is widely used to assess the sexual recidivism risk of sex offenders. It is frequently applied in jurisdictions as a decision-making tool for release or indefinite admission to a psychiatric hospital within the jail of sex offenders. The decision to release or retain a criminal depends solely on the total score which is considered as the only independent variable. In our study, two models of Static 99R are considered: the 5-year high risk model and the 10-year high risk model. To identify the most appropriate threshold, we performed four independent methods. These are: the point closest-to-(0,1), the concordance probability (CZ), the index of union (IU), and the plot of sensitivity versus specificity. Remarkably, all four methods yielded identical results. For the 5-year high risk model, the optimal threshold is 0.184, which corresponds to a cut-off score of 5. Consequently, a score of 5 or higher implies that the offender is very likely to recidivate. Similarly, for the 10-year high risk, the optimal threshold is 0.293 which corresponds also to a cut-off score of 5.
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